A Genomic Perspective on Pathogen Adaptation to Antibiotics and Vaccines

Among human pathogens, Streptococcus pneumoniae holds an especially prominent place in the history of biomedical investigation.  Griffith (1928) described the transforming principle, a soluble substance released by dead, virulent pneumococci that could render living avirulent pneumococci able to effectively kill a mouse.  Oswald Avery’s commitment to curing pneumococcal pneumonia (http://profiles.nlm.nih.gov/ps/retrieve/Narrative/CC/p-nid/37) led him and his collaborators to determine that the pneumococcal transforming principle was DNA (Avery et al., 1944).  It was also Avery’s and his collaborators’ work on pneumococci that provided some of the first insights into the chemical nature of most bacterial capsules. (more…)

Amino Acid Gymnastics and the Evolution of Influenza Virus Resistance to Oseltamivir

In previous posts, I discussed, respectively, the use of selection to generate an antibody of potential value in treating influenza A virus infections (1) and the relevance of protein dynamics to the evolution of protein function (2).   A recent paper in Science (3) offers evidence suggesting that internal protein dynamics play a crucial role in shaping the evolution and spread of resistance to the influenza neuraminidase inhibitor, oseltamivir (Tamiflu®). (more…)

Out of Jerusalem

The human haplotype map (HapMap) shows that human populations differ genetically and have been subject to strong, recent positive selection: selection ‘for’ particular genetic variants. Surprisingly, patterns of inferred selection vary markedly between the three human groups analyzed thus far, one Caucasian, one African, and one Asian (Voight et al. 2006). Ethnicity, and natural selection, may thus play stronger roles in diverse human traits, including genetic susceptibility to disease, than previously believed.

One ethnic group, famous for reasons including its high incidence of otherwise-rare diseases, is the Ashkenazi. The concentration of recessive diseases in this group has usually been attributed to founder events, but this interpretation has been challenged (more…)

Evolutionary pharmacogenomics

Articles about evolution and medicine are spread so widely over the scientific landscape that no matter how much you read, you know you are missing things. The pleasure on finding them is, however, like finding a diamond in the sand. Such is the case with evolutionary pharmacogenomics (a phrase that turns up not one hit on Goggle!). At our seminar yesterday, Mark Thomas put us onto work by Daniel Nebert. A long-time leader in pharmacogenomics, he has written several papers offering an evolutionary framework for thinking about genes that influence drug metabolism. Suddenly, all kinds of things make sense. (more…)